Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a severe complication associated with prolonged dexamethasone (DEX) treatment. Excessive glucocorticoid exposure induces osteoblast apoptosis, suppresses osteogenic differentiation, and disrupts osteogenesis–angiogenesis coupling. Therefore, strategies that restore osteoblast and vascular function are needed. In this study, we evaluated the protective effects of CPS-5, a natural coumarin compound, in a DEX-induced in vitro model mimicking GIONFH conditions. Osteoblasts and endothelial cells were treated with DEX to induce dysfunction. Cell viability and apoptosis were assessed by MTT assay and JC-1/PI staining. Osteogenic differentiation was analyzed using Western blotting, ALP activity, and Alizarin Red S staining. CPS-5 significantly reduced DEX-induced apoptosis and restored osteogenic differentiation by increasing ALP activity and RUNX2 expression. CPS-5 also enhanced angiogenesis and type H vessel related factors, including VEGFA and PDGFRβ. Conditioned medium from CPS-5 treated osteoblasts promoted endothelial cell proliferation and migration, indicating improved osteogenesis–angiogenesis coupling. Additionally, CPS-5 directly improved endothelial function by increasing VEGFA and type H vessel markers. These findings demonstrate that CPS-5 alleviates DEX induced osteoblastic and endothelial dysfunction and restores osteogenesis–angiogenesis coupling, suggesting its therapeutic potential for GIONFH.